tbuckley/cabot-search huggingface dataset:
Evaluating large language models on medical evidence summarization
Authors: Liyan Tang, Zhaoyi Sun, Betina Idnay, Jordan G. Nestor, Ali Soroush, Pierre A. Elias, Ziyang Xu, Ying Ding, Greg Durrett, Justin F. Rousseau, Chunhua Weng, Yifan Peng
Journal: npj Digital Medicine (2023)

Abstract Recent advances in large language models (LLMs) have demonstrated remarkable successes in zero- and few-shot performance on various downstream tasks, paving the way for applications in high-stakes domains. In this study, we systematically examine the capabilities and limitations of LLMs, specifically GPT-3.5 and ChatGPT, in performing zero-shot medical evidence summarization across six clinical domains. We conduct both automatic and human evaluations, covering several dimensions of summary quality. Our study demonstrates that automatic metrics often do not strongly correlate with the quality of summaries. Furthermore, informed by our human evaluations, we define a terminology of error types for medical evidence summarization. Our findings reveal that LLMs could be susceptible to generating factually inconsistent summaries and making overly convincing or uncertain statements, leading to potential harm due to misinformation. Moreover, we find that models struggle to identify the salient information and are more error-prone when summarizing over longer textual contexts.
Direct and quantitative assessments of near-infrared light attenuation and spectroscopic detection depth in biological tissues using surface-enhanced Raman scattering
Authors: Li Lin, Haoqi He, Ruiyang Xue, Yumin Zhang, Ziwen Wang, Shuming Nie, Jian Ye
Journal: Med-X (2023)

Abstract Optical imaging and spectroscopic modalities are of broad interest for in-vivo molecular imaging, fluorescence guided cancer surgery, minimally invasive diagnostic procedures, and wearable devices. However, considerable debate still exists as to how deeply visible and near-infrared (NIR) light could penetrate normal and diseased tissues under clinically relevant conditions. Here we report the use of surface-enhanced Raman scattering (SERS) nanotags embedded in ex-vivo animal tissues for direct and quantitative measurements of light attenuation and spectroscopic detection depth at both the NIR-I and NIR-II spectral windows. SERS nanotags are well suited for this purpose because of their sharp spectral features that can be accurately differentiated from fluorescence and background emission. For the first time, the spectroscopic detection depth is quantitatively defined and measured as the maximal thickness of tissues through which the embedded SERS nanotags are still detected at a signal-to-noise ratio (SNR) of three (99.7% confidence level). Based on data from six types of fresh ex-vivo tissues (brain, kidney, liver, muscle, fat, and skin), we find that the maximum detection depth values range from 1—3 mm in the NIR-I window, to 3—6 mm in the NIR-II window. The depth values are largely determined by two factors – the intrinsic optical properties of the tissue, and the overall SNRs of the system without the tissue (system SNR, a result of nanotag brightness, instrument efficiency, and data acquisition parameters). In particular, there is an approximately linear-logarithmic relationship between the system SNR and maximum detection depth. Thus, the detection of hidden or occult lesions can be improved by three strategies – reducing tissue attenuation, minimizing background noise, and maximizing the system’s performance as judged by SNR. Graphical Abstract
Use of Nirsevimab for the Prevention of Respiratory Syncytial Virus Disease Among Infants and Young Children: Recommendations of the Advisory Committee on Immunization Practices — United States, 2023
Authors: Jefferson M. Jones, Katherine E. Fleming-Dutra, Mila M. Prill, Lauren E. Roper, Oliver Brooks, Pablo J. Sánchez, Camille N. Kotton, Barbara E. Mahon, Sarah Meyer, Sarah S. Long, Meredith L. McMorrow
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

Respiratory syncytial virus (RSV) is the leading cause of hospitalization among U.S. infants. In July 2023, the Food and Drug Administration approved nirsevimab, a long-acting monoclonal antibody, for passive immunization to prevent RSV-associated lower respiratory tract infection among infants and young children. Since October 2021, the Advisory Committee on Immunization Practices (ACIP) Maternal and Pediatric RSV Work Group has reviewed evidence on the safety and efficacy of nirsevimab among infants and young children. On August 3, 2023, ACIP recommended nirsevimab for all infants aged <8 months who are born during or entering their first RSV season and for infants and children aged 8-19 months who are at increased risk for severe RSV disease and are entering their second RSV season. On the basis of pre-COVID-19 pandemic patterns, nirsevimab could be administered in most of the continental United States from October through the end of March. Nirsevimab can prevent severe RSV disease among infants and young children at increased risk for severe RSV disease.
Fully Closed-Loop Glucose Control Compared With Insulin Pump Therapy With Continuous Glucose Monitoring in Adults With Type 1 Diabetes and Suboptimal Glycemic Control: A Single-Center, Randomized, Crossover Study
Authors: Charlotte K. Boughton, Sara Hartnell, Rama Lakshman, Munachiso Nwokolo, Malgorzata E. Wilinska, Julia Ware, Janet M. Allen, Mark L. Evans, Roman Hovorka
Journal: Diabetes Care (2023)

We evaluated the safety and efficacy of fully closed-loop with ultrarapid insulin lispro in adults with type 1 diabetes and suboptimal glycemic control compared with insulin pump therapy with continuous glucose monitoring (CGM).This single-center, randomized, crossover study enrolled 26 adults with type 1 diabetes using insulin pump therapy with suboptimal glycemic control (mean ± SD, age 41 ± 12 years, HbA1c 9.2 ± 1.1% [77 ± 12 mmol/mol]). Participants underwent two 8-week periods of unrestricted living to compare fully closed-loop with ultrarapid insulin lispro (CamAPS HX system) with insulin pump therapy with CGM in random order.In an intention-to-treat analysis, the proportion of time glucose was in range (primary end point 3.9-10.0 mmol/L) was higher during closed-loop than during pump with CGM (mean ± SD 50.0 ± 9.6% vs. 36.2 ± 12.2%, mean difference 13.2 percentage points [95% CI 9.5, 16.9], P < 0.001). Time with glucose >10.0 mmol/L and mean glucose were lower during closed-loop than during pump with CGM (mean ± SD time >10.0 mmol/L: 49.0 ± 9.9 vs. 62.9 ± 12.6%, mean difference -13.3 percentage points [95% CI -17.2, -9.5], P < 0.001; mean ± SD glucose 10.7 ± 1.1 vs. 12.0 ± 1.6 mmol/L, mean difference -1.2 mmol/L [95% CI -1.8, -0.7], P < 0.001). The proportion of time with glucose <3.9 mmol/L was similar between periods (median [interquartile range (IQR)] closed-loop 0.88% [0.51-1.55] vs. pump with CGM 0.64% [0.28-1.10], P = 0.102). Total daily insulin requirements did not differ (median [IQR] closed-loop 51.9 units/day [35.7-91.2] vs. pump with CGM 50.7 units/day [34.0-70.0], P = 0.704). No severe hypoglycemia or ketoacidosis occurred.Fully closed-loop insulin delivery with CamAPS HX improved glucose control compared with insulin pump therapy with CGM in adults with type 1 diabetes and suboptimal glycemic control.
Lineage-specific detection of residual disease predicts relapse in patients with chronic myeloid leukemia stopping therapy
Authors: Ilaria S. Pagani, Naranie Shanmuganathan, Phuong Dang, Verity A. Saunders, Randall Grose, Chung H. Kok, Jane James, Molly Tolland, Jodi A. Braley, Haley K. Altamura, David T. Yeung, Susan Branford, Agnes S. M. Yong, Timothy P. Hughes, David M. Ross
Journal: Blood (2023)
Aptamers in neuro-oncology: An emerging therapeutic modality
Authors: Caroline Doherty, Brandon Wilbanks, Soumen Khatua, Louis James Maher
Journal: Neuro-Oncology (2023)

Abstract Despite recent advances in the understanding of brain tumor pathophysiology, challenges associated with tumor location and characteristics have prevented significant improvement in neuro-oncology therapies. Aptamers are short, single-stranded DNA or RNA oligonucleotides that fold into sequence-specific, 3-dimensional shapes that, like protein antibodies, interact with targeted ligands with high affinity and specificity. Aptamer technology has recently been applied to neuro-oncology as a potential approach to innovative therapy. Preclinical research has demonstrated the ability of aptamers to overcome some obstacles that have traditionally rendered neuro-oncology therapies ineffective. Potential aptamer advantages include their small size, ability in some cases to penetrate the blood-brain barrier, inherent lack of immunogenicity, and applicability for discovering novel biomarkers. Herein, we review recent reports of aptamer applications in neuro-oncology including aptamers found by cell- and in vivo- Systematic Evolution of Ligands by Exponential Enrichment approaches, aptamer-targeted therapeutic delivery modalities, and aptamers in diagnostics and imaging. We further identify crucial future directions for the field that will be important to advance aptamer-based drugs or tools to clinical application in neuro-oncology.
P04 Biologics combined with conventional systemic agents for the treatment of children with severe psoriasis: practice survey among French and Italian paediatric dermatologists
Authors: Emmanuel Mahé, Vito di Lernia
Journal: British Journal of Dermatology (2023)

Abstract Combined therapies involve the use of multiple drugs to increase efficacy and reduce the toxicity of individual treatments. We performed a survey carried out among French and Italian paediatric dermatologists (SFPD, GrPso, SIDerP) to better understand the reasons for using or avoiding these combinations. The survey was completed by 61 paediatric dermatologists (France, 57.4%; Italy, 42.6%; hospital practice, 98.4%; members of societies of paediatric societies and/or psoriasis working groups, 73.8%). Thirty-nine (63.9%) had previously used or planned to use the combined therapies, most commonly TNF-α inhibitors with acitretin or methotrexate. The most common reasons for dermatologists not using combined therapies were a lack of information about the safety (27.3%) or effectiveness (22.7%) of the combinations and the absence of recommendations on how to use combined therapies (22.7%). The main reason for using these treatments was to improve the outcome of biologic therapies in cases of partial efficacy or loss of efficacy. The most frequent clinical situations in which the dermatologists indicated that they combined therapies were to control a loss of efficacy (82.1%) and to treat psoriasis flare-ups (51.3%). Combined therapies have been used by the majority of paediatric dermatologists in the treatment of childhood psoriasis. Absence of information about these combined therapies, and no guidelines about their use are major limits for their use. However, these combined therapies should be considered for the treatment of children with severe psoriasis, psoriatic arthritis and recalcitrant disease. Their use needs to be clarified in future management guidelines.
O04 Segmental congenital haemangioma: a novel subtype of a rare vascular tumour
Authors: Jadesola Oyedepo, Mary Glover, Claire O’Neill, Satyamaanasa Polubothu, Lea Solman
Journal: British Journal of Dermatology (2023)

Abstract Congenital haemangiomas (CH) are rare vascular tumours present at birth. These high-flow vascular lesions can lead to significant morbidity secondary to high-output cardiac failure (HOCF) and Kasabach–Merritt phenomenon (KMP). They are classically round/oval lesions and present anywhere on the body. The majority involute spontaneously in the first 2 years of life. We describe three patients who presented with an unusual segmental pattern CH of the head/scalp: the first with a segmental CH of the left forehead, extending over the left eye with associated ipsilateral heterochromia and anisocoria; the second with a segmental ulcerated CH of the right scalp – catastrophic haemorrhage from the CH sadly resulted in death at age 6 weeks; the third with a left forehead segmental CH. None of the CH in this series developed HOCF or KMP. All lesions were consistent with CH on sonography and histology where available. Patients 1 and 3 exhibited spontaneous involution in the first 2 years of life. Segmental CH have been reported once before in a series of three patients, although involving the arm/trunk rather than the head. Two of the three patients developed KMP/HOCF. The genetic basis in this cohort was identical to that of classic nonsegmental CH, activating somatic mutations in GNAQ/11. The striking segmental pattern in our cohort is likely attributable to the timing of the somatic hit during development. Identification of this pattern in CH gives important insights into vascular tumorigenesis. Further cohort studies are needed to determine if this group has differing clinical outcomes from classical CH.
O02 A case for diagnosis: ectodermal dysplasia and severe myelodysplasia
Authors: Cathal O’Connor, John Bourke
Journal: British Journal of Dermatology (2023)

Abstract A 13-year-old girl was referred to us by our paediatric colleagues due to vulval dermatitis. She had a history of congenital hypotrichosis, microcephaly, abnormal dentition, dyshidrosis manifest as recurrent febrile seizures in infancy, recurrent infections, neutropaenia and macrocytosis. Her father and younger brother have a similarly striking phenotype, with complete absence of scalp and body hair, abnormal teeth, abnormal sweating, but normal nails. In addition, the father has required a stem cell transplant for myelodysplastic syndrome. None of the family have keratoderma, cleft palate, ectrodactyly or cardiomyopathy. DNA from our index patient was sent to Cardiff for the ectodermal dysplasia (ED) plus 70 gene panel for next-generation sequencing, but no mutation was found. Our paediatric haematology colleagues sequentially arranged dyskeratosis congenita panel, myeloid panel, and whole-exome sequencing for the younger brother, which did not identify a causative mutation. Unusually, all three were found to have mosaic trisomy 18. The transmission of trisomy 18 from parent to child as a mosaic trait in both generations is extremely unusual, and mosaic trisomy 18 has not been previously reported to cause ED. We would appreciate any input on a genetic diagnosis for this family with a distinctive phenotype consistent with hypohidrotic ED associated with myelodysplasia, with extensive genetic testing revealing a potentially spurious or coincidental mosaic trisomy 18 in all three affected family members.
Gastrointestinal syndromes preceding a diagnosis of Parkinson’s disease: testing Braak’s hypothesis using a nationwide database for comparison with Alzheimer’s disease and cerebrovascular diseases
Authors: Bo Konings, Luisa Villatoro, Jef Van den Eynde, Guillermo Barahona, Robert Burns, Megan McKnight, Ken Hui, Gayane Yenokyan, Jan Tack, Pankaj Jay Pasricha
Journal: Gut (2023)

Objective Braak’s hypothesis states that Parkinson’s disease (PD) originates in the gastrointestinal (GI) tract, and similar associations have been established for Alzheimer’s disease (AD) and cerebrovascular diseases (CVD). We aimed to determine the incidence of GI syndromes and interventions preceding PD compared with negative controls (NCs), AD and CVD. Design We performed a combined case-control and cohort study using TriNetX, a US based nationwide medical record network. Firstly, we compared subjects with new onset idiopathic PD with matched NCs and patients with contemporary diagnoses of AD and CVD, to investigate preceding GI syndromes, appendectomy and vagotomy. Secondly, we compared cohorts with these exposures to matched NCs for the development of PD, AD and CVD within 5 years. Results We identified 24 624 PD patients in the case-control analysis and matched 18 cohorts with each exposure to their NCs. Gastroparesis, dysphagia, irritable bowel syndrome (IBS) without diarrhoea and constipation showed specific associations with PD (vs NCs, AD and CVD) in both the case-control (odds ratios (ORs) vs NCs 4.64, 3.58, 3.53 and 3.32, respectively, all p&lt;0.0001) and cohort analyses (relative risks (RRs) vs NCs 2.43, 2.27, 1.17 and 2.38, respectively, all p&lt;0.05). While functional dyspepsia, IBS with diarrhoea, diarrhoea and faecal incontinence were not PD specific, IBS with constipation and intestinal pseudo-obstruction showed PD specificity in the case-control (OR 4.11) and cohort analysis (RR 1.84), respectively. Appendectomy decreased the risk of PD in the cohort analysis (RR 0.48). Neither inflammatory bowel disease nor vagotomy were associated with PD. Conclusion Dysphagia, gastroparesis, IBS without diarrhoea and constipation might specifically predict Parkinson’s disease.
O07 Faceless PHACES
Authors: Henrietta Albela, Claire O’Neill, Mary Glover, Lea Solman, Satyamaanasa Polubothu
Journal: British Journal of Dermatology (2023)

Abstract PHACES syndrome (posterior fossa – haemangioma – arterial – cardiac – eye – sternal) is a multisystem disorder which often presents first with a facial, segmental infantile haemangioma (IH). Prompt recognition of this subtype of IH is key to enable early detection of neurological/ophthalmological/cardiac anomalies. As per international consensus guidelines, the presence of a facial segmental haemangioma &amp;gt; 5 cm triggers screening for associated extracutaneous anomalies. We present three infants with absent/minimal facial haemangioma, but who fulfilled extracutaneous criteria of PHACES syndrome. Patient 1 was a 3-week-old female who presented with a 1–2-cm linear superficial left post-auricular IH. PHACES screening revealed an atrial septal defect, intracranial haemangiomas and hypoplastic cerebrovasculature. Patient 2, a 9-month-old girl, was admitted to intensive care following acute respiratory deterioration. Examination revealed a segmental IH of the occipital scalp. PHACES screening revealed a vascular ring, right aortic arch, aberrant subclavian artery, subglottic and mediastinal IH and narrowing/tortuosity of the left internal carotid artery. Patient 3, a 4-month-old male, was referred for evaluation of three superficial IH, all &amp;lt; 0.5 cm, one on the right post-auricular skin and two on the right forehead. He suffered acute collapse at 2 weeks of life leading to a diagnosis of obstructed total anomalous pulmonary–venous connection requiring emergency surgical correction. PHACES screening revealed bilateral dysplastic/torturous internal carotid arteries. We present three cases of PHACES syndrome without the classic facial segmental IH. Clinicians should be aware of the spectrum of IH observed in PHACES syndrome to enable prompt screening of those presenting with atypical scalp and post-auricular lesions.
P18 Epidermolysis bullosa acquisita in children: report of three cases
Authors: Maria L Bageta, Eliana Cella, A Bettina Cervini, Maria del Valle Centeno, Liliana Roquel, John Mee, Richard Groves, Eduardo Calonje, Richard G Goodwin, Jemima Mellerio, Gabriela Petrof, Anna E Martinez
Journal: British Journal of Dermatology (2023)

Abstract Epidermolysis bullosa acquisita (EBA) is an acquired, subepidermal blistering skin disease characterized by autoantibodies against type VII collagen, which links the epidermis to the dermis at the dermo-epidermal junction. Clinically, patients have skin fragility and blisters over trauma-prone sites, scarring, milia and onychodystrophy. The diagnosis can be challenging as it shares clinical and histopathological features with other immunobullous diseases. Although exceptionally rare in children, we report three paediatric patients with EBA and variable disease severity. The main clinical features were blisters (n = 3), milia (n = 3), scarring (n = 2), oral erosions (n = 2) and onychodystrophy (n = 1). Histological findings were nonspecific, showing a subepidermal blister with various inflammatory infiltrates. On direct immunofluorescence a bright deposit of IgG was seen, and the antibodies adhered to the dermal side of the salt-split in two cases. ELISA analysis confirmed circulating autoantibodies against type VII collagen in one patient. All received a course of oral corticosteroids alongside steroid-sparing agents such as dapsone, azathioprine and rituximab depending on clinical response and shared favourable prognosis. Early use of topical steroids can help but high-dose oral corticosteroids are often required as well as steroid-sparing agents such as dapsone, methotrexate, azathioprine, ciclosporin, mycophenolate mofetil, cyclophosphamide and rituximab. In our experience, although the treatment approaches have been different, all the patients had favourable outcomes.
Targeted High-throughput Sequencing for Hematological Malignancies: A GBMHM Survey of Practice and Cost Evaluation in France
Authors: Meryl Darlington, Pierre Sujobert, Olivier Kosmider, Damien Luque Paz, Sophie Kaltenbach, Martin Figeac, Sandrine Hayette, Nadia Mezaour, Séverine Coquerelle, Anne-Sophie Alary, Audrey Bidet, Yannick Le Bris, Eric Delabesse, Frédéric Davi, Claude Preudhomme, Isabelle Durand-Zaleski, Elizabeth Macintyre
Journal: HemaSphere (2023)

The objective of this study was to assess the clinical impact and financial costs of next-generation sequencing (NGS) in 5 categories of pediatric and adult hematological cancers. NGS prescriptions were prospectively collected from 26 laboratories, with varied technical and reporting practice (all or only significant targets). Impact was defined by the identification of (1) an actionable mutation, (2) a mutation with prognostic and/or theranostic value, and/or (3) a mutation allowing nosological refinement, reported by local investigators. A microcosting study was undertaken in 4 laboratories, identifying the types and volumes of resources required for each procedural step. Individual index prescriptions for 3961 patients were available for impact analysis on the management of myeloid disorders (two thirds) and, mainly mature B, lymphoid disorders (one third). NGS results were considered to impact the management for 73.4% of prescriptions: useful for evaluation of prognostic risk in 34.9% and necessary for treatment adaptation (actionable) in 19.6%, but having no immediate individual therapeutic impact in 18.9%. The average overall cost per sample was 191 € for the restricted mature lymphoid amplicon panel. Capture panel costs varied from 369 € to 513 €. Unit costs varied from 0.5 € to 5.7 € per kb sequenced, from 3.6 € to 11.3 € per target gene/hot-spot sequenced and from 4.3 € to 73.8 € per target gene/hot-spot reported. Comparable costs for the Amplicon panels were 5–8 € per kb and 10.5–14.7 € per target gene/hot-spot sequenced and reported, demonstrating comparable costs with greater informativity/flexibility for capture strategies. Sustainable funding of precision medicine requires a transparent discussion of its impact on care pathways and its financial aspects.